Synthesis of Antimicrobial Lipopeptides Using the "CLipPA" Thiol-Ene Reaction

Methods Mol Biol. 2020;2103:263-274. doi: 10.1007/978-1-0716-0227-0_18.


Cysteine Lipidation on a Peptide or Amino acid (CLipPA) technology provides a facile method for the lipidation of unprotected peptides containing a free thiol group by using a "click" radical-initiated thiol-ene reaction to effect addition to a vinyl ester. The methodology is highly versatile, leading to high conversion rates while maintaining excellent chemoselectivity and tolerance for a large variety of peptide substrates and functional groups. Herein we describe the simple general procedure for the synthesis of a focused library of bioactive S-lipidated antimicrobial peptides via late-stage derivatization using solution-phase CLipPA lipidation.

Keywords: Antimicrobial peptides; CLipPA; Click chemistry; Lipopeptides; Peptide lipidation; Peptide synthesis; Thiol-ene reaction.

MeSH terms

  • Amino Acids / chemistry*
  • Anti-Infective Agents / chemical synthesis*
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / isolation & purification
  • Antimicrobial Cationic Peptides / chemical synthesis
  • Chemistry Techniques, Synthetic*
  • Chromatography, High Pressure Liquid
  • Click Chemistry*
  • Lipopeptides / chemical synthesis*
  • Lipopeptides / chemistry
  • Lipopeptides / isolation & purification
  • Molecular Structure
  • Solvents
  • Sulfhydryl Compounds / chemistry


  • Amino Acids
  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Lipopeptides
  • Solvents
  • Sulfhydryl Compounds